Cross talk between neuroregulatory molecule and monocyte: nerve growth factor activates the inflammasome.
Cross talk between neuroregulatory molecule and monocyte: nerve growth factor activates the inflammasome.
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DOI：
10.1371/journal.pone.0121626
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Raychaudhuri SP
中科院分区：
文献类型：
--
作者：
Datta-Mitra A;Kundu-Raychaudhuri S;Mitra A;Raychaudhuri SP
越来越多的证据表明，神经元外神经生长因子(NGF)在获得性免疫反应中发挥了作用。然而，关于其在先天性免疫中的作用和潜在机制的信息很少。先天免疫在自身免疫性疾病中的作用变得越来越重要。在这项研究中，我们探讨了多效性神经生长因子在先天性免疫反应中的作用及其与IL-1β分泌有关的潜在分子机制。人单核细胞、Null和NLRP3缺陷型THP-1细胞用于此目的。从蛋白和β水平检测神经生长因子对IL-1基因表达的影响。为探讨NGF对NLRP1/NLRP3炎性小体作用的分子机制，采用ELISA法、免疫荧光法、流式细胞仪和实时定量聚合酶链式反应(Real-time PCR)检测NGF对NLRP1/NLRP3炎性小体及其下游关键蛋白激活的caspase-1的影响。在人单核细胞和空THP-1细胞系中，神经生长因子通过其受体TrkA显著上调IL-1β的表达，并依赖于Caspase-1。此外，我们观察到，神经生长因子通过NLRP1/NLRP3炎症体诱导Caspase-1的激活，并且依赖于主要的转录因子-κB。据我们所知，这是第一个关于神经调节分子Ngf在先天性免疫反应中的机制方面的报道，从而丰富了我们对其在炎症中的致病作用的理解。这些观察为自身免疫性疾病的抗神经生长因子治疗提供了进一步的证据，也开启了神经生长因子在IL-1β介导的疾病中作用的新的研究领域。
Increasing evidence points to a role for the extra-neuronal nerve growth factor (NGF) in acquired immune responses. However, very little information is available about its role and underlying mechanism in innate immunity. The role of innate immunity in autoimmune diseases is becoming increasingly important. In this study, we explored the contribution of pleiotropic NGF in the innate immune response along with its underlying molecular mechanism with respect to IL-1β secretion. Human monocytes, null and NLRP3 deficient THP-1 cell lines were used for this purpose. We determined the effect of NGF on secretion of IL-1β at the protein and mRNA levels. To determine the underlying molecular mechanism, the effect of NGF on NLRP1/NLRP3 inflammasomes and its downstream key protein, activated caspase-1, were evaluated by ELISA, immunoflorescence, flow cytometry, and real-time PCR. In human monocytes and null THP-1 cell line, NGF significantly upregulates IL-1β at protein and mRNA levels in a caspase-1 dependent manner through its receptor, TrkA. Furthermore, we observed that NGF induces caspase-1 activation through NLRP1/NLRP3 inflammasomes, and it is dependent on the master transcription factor, NF-κB. To best of our knowledge, this is the first report shedding light on the mechanistic aspect of a neuroregulatory molecule, NGF, in innate immune response, and thus enriches our understanding regarding its pathogenic role in inflammation. These observations add further evidence in favor of anti-NGF therapy in autoimmune diseases and also unlock a new area of research about the role of NGF in IL-1β mediated diseases.
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影响因子：
6.5
作者：
Kennedy-Crispin, Milene;Billick, Erika;Mitsui, Hiroshi;Gulati, Nicholas;Fujita, Hideki;Gilleaudeau, Patricia;Sullivan-Whalen, Mary;Johnson-Huang, Leanne M.;Suarez-Farinas, Mayte;Krueger, James G.
通讯作者：
Krueger, James G.
影响因子：
3
作者：
Aloe, L
通讯作者：
Aloe, L
影响因子：
4.4
作者：
Kumar, Himanshu;Kumagai, Yutaro;Kawai, Taro
通讯作者：
Kawai, Taro
影响因子：
2.1
作者：
Loh, N. K.;Lucas, M.;Prentice, D.
通讯作者：
Prentice, D.
影响因子：
3.7
作者：
Lasiglie, Denise;Traggiai, Elisabetta;Gattorno, Marco
通讯作者：
Gattorno, Marco